Our research aims to translate and evaluate the recently developed pH weighted MRI as a new imaging parameter for characterizing acute human ischemic stroke. Since the 1990s, there has been enormous advancement in stroke therapeutics and imaging, but early intervention is required for successful outcome. For instance, the conventional treatment window for recombinant tissue plasminogen activator (tPA) is within 3 hrs of stroke onset, which significantly limits its clinical applications. On the other hand, could salvageable ischemic tissue be detected, the thrombolytic therapy can be individualized to benefit patients admitted beyond the traditional treatment window. MRI, particularly perfusion and diffusion MRI, may highlight potentially salvageable ischemic tissue for treatment, and is being used as operational penumbra. However, the mismatch model is not optimal;portions of the diffusion lesion can be reversed by early reperfusion, while the perfusion deficit may contain hypoperfused area at no risk of infarction. Consequently, the development of reliable and specific imaging markers for salvageable tissue that complement perfusion and diffusion MRI, will be extremely valuable. pH, a tightly regulated tissue parameter, falls sharply upon metabolic impairment and may potentially serve as a sensitive metabolic marker for ischemic tissue. The proposed work will test whether a recently developed pH weighted MRI technique (amide proton transfer (APT) imaging) can become a new imaging marker for identifying early ischemic tissue. Previously, we have shown that pH weighted imaging provides information complementary to that attained by perfusion and diffusion MRI;the outer boundary of the hypoperfused area showing a decrease in pH without diffusion abnormality may correspond to ischemic penumbra, while the hypoperfused region at normal pH may represent benign oligemia. In addition, the final infarction area was not different from the pH weighted MRI deficit (p=0.84), but significantly different from the perfusion and diffusion MRI (p<0.001) using a permanent animal stroke model. In the proposed research, we will perform a pilot study to translate and evaluate pH weighted MRI for human acute ischemic stroke and our specific aims are: (1) to implement and optimize a fast multi-slice pH weighted MRI on clinical scanners (2) to evaluate pH weighted MRI as a new imaging marker complementary to perfusion and diffusion MRI. We hypothesize the pH weighted MRI will improve the diagnostic value of multi-parametric MRI and assist with image-guided stroke therapy. PUBLIC HEALTH RELEVANCE: Ischemic stroke is a severe neurological disease with profound health and socioeconomic impact. The key for effective stroke therapy is to salvage ischemic tissue before it is irreversibly damaged. We propose to translate and evaluate the recently developed pH weighted MRI as a new imaging marker for human ischemic tissue, which has potential to improve the diagnostic value of MRI and assist with image-guided stroke therapy.